Mitotane reduces human and mouse ACTH-secreting pituitary cell viability and function

Gentilin, Erica; Tagliati, Federico; Terzolo, Massimo; Zoli, Matteo; Lapparelli, Marcello; Minoia, Mariella; Ambrosio, Maria Rosaria; Uberti, Ettore C. degli; Zatelli, Maria Chiara

doi:10.1530/joe-13-0210

Cited by 24 publications

(15 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitotane was of higher importance in the earlier period of our study before the development of targeted pituitary-directed medications. In addition to its well known adrenolytic ac- tivity, there are published data supporting potential action on a pituitary level [50]. All our patients treated with an adjuvant therapy with mitotane after PRT or TSA achieved a remission.…”

Section: Blockers Of Steroidogenesissupporting

confidence: 55%

Cushing’s Syndrome: A Historic Review of the Treatment Strategies and Corresponding Outcomes in a Single Tertiary Center over the Past Half-Century

et al. 2018

View full text Add to dashboard Cite

Cushing's syndrome (CS) is associated with serious comorbidities and an increased mortality rate that could be reduced only if strict biochemical control is achieved. The aim of this study was to show the 50-year experience of a single tertiary center in the management of CS patients - the different treatment modalities used over the years and the corresponding outcomes. It was a retrospective study of a large cohort of patients from the Bulgarian CS database: 613 patients (374 with ACTH-dependent and 239 with ACTH-independent CS). Pituitary surgery was applied to 242 patients with Cushing's disease (CD) with initial remission rate of 74% of which 10% relapsed. Approximately 36% manifested with active disease during the long-term follow-up (26% with persistent disease, 10% relapses) most of which were subjected to a secondary treatment (13.6% to pituitary resurgery, 14% to pituitary radiotherapy, and 5.4% to bilateral adrenalectomy). A total of 294 CD patients received medical therapy with overall remission rates for the most commonly used drugs: dopamine agonists 20%, pasireotide 30%, and ketoconazole 63%. Significant improvement of results was achieved by combining drugs with different mechanisms of action. Regardless of the progress in the neurosurgery and radiotherapy techniques and new drugs discovery, the management of patients with CS remains a real challenge for physicians. Not only patients with adrenal carcinoma but also significant percentage of subjects with persistent and recurrent Cushing's disease often require a polymodal approach and the efforts of a multidisciplinary highly qualified, experienced, and motivated team in order to achieve a long-term remission.

show abstract

Section: Blockers Of Steroidogenesissupporting

confidence: 55%

Cushing’s Syndrome: A Historic Review of the Treatment Strategies and Corresponding Outcomes in a Single Tertiary Center over the Past Half-Century

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The effect of Staurosporine, a well known apoptotic stimulus, on cell viability was assessed by measuring cellular ATP levels using the ATPLite luminescence-based assay (PerkinElmer, Waltham, MA, USA) following manufacturer’s instructions and reading the plate with the EnVision Multilabel Reader (PerkinElmer) as previously described [16,17]. Briefly, 2 x 10 4 cells/ well were plated in optically clear 96-well black plates (Costar #3904, Corning, NY, USA) and incubated overnight at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Magmas Overexpression Inhibits Staurosporine Induced Apoptosis in Rat Pituitary Adenoma Cell Lines

et al. 2013

Self Cite

View full text Add to dashboard Cite

Magmas is a nuclear gene that encodes for the mitochondrial import inner membrane translocase subunit Tim16. Magmas is overexpressed in the majority of human pituitary adenomas and in a mouse ACTH-secreting pituitary adenoma cell line. Here we report that Magmas is highly expressed in two out of four rat pituitary adenoma cell lines and its expression levels inversely correlate to the extent of cellular response to staurosporine in terms of apoptosis activation and cell viability. Magmas over-expression in rat GH/PRL-secreting pituitary adenoma GH4C1 cells leads to an increase in cell viability and to a reduction in staurosporine-induced apoptosis and DNA fragmentation, in parallel with the increase in Magmas protein expression. These results indicate that Magmas plays a pivotal role in response to pro-apoptotic stimuli and confirm and extend the finding that Magmas protects pituitary cells from staurosporine-induced apoptosis, suggesting its possible involvement in pituitary adenoma development.

show abstract

“…ACTH levels were found to be scattered with great individual variations. More recently, Gentilin et al (17) showed that mitotane was able to affect corticotroph function and cell survival in the mouse pituitary cell line AtT20/D16v-F2 and in the primary cultures of human ACTH-secreting pituitary adenomas. Mitotane reduced cell viability and ACTH secretion by blocking the stimulatory effects of corticotropin releasing hormone (CRH) on cell viability, ACTH secretion and POMC expression.…”

Section: Introductionmentioning

confidence: 99%

Effects of mitotane on the hypothalamic–pituitary–adrenal axis in patients with adrenocortical carcinoma

Reimondo

Puglisi

Zaggia

et al. 2017

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

The observation of lower ACTH levels in patients with ACC than that in patients with PAI, both in basal conditions and after CRH stimulation, suggests that mitotane may play an inhibitory effect on ACTH secretion at the pituitary levels. In conclusion, the present study shows that mitotane affects the HPA axis at multiple levels and no single biomarker may be used for the assessment of adrenal insufficiency.

show abstract

Mitotane reduces human and mouse ACTH-secreting pituitary cell viability and function

Cited by 24 publications

References 38 publications

Cushing’s Syndrome: A Historic Review of the Treatment Strategies and Corresponding Outcomes in a Single Tertiary Center over the Past Half-Century

Cushing’s Syndrome: A Historic Review of the Treatment Strategies and Corresponding Outcomes in a Single Tertiary Center over the Past Half-Century

Magmas Overexpression Inhibits Staurosporine Induced Apoptosis in Rat Pituitary Adenoma Cell Lines

Effects of mitotane on the hypothalamic–pituitary–adrenal axis in patients with adrenocortical carcinoma

Contact Info

Product

Resources

About